Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis(RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long?term extension(LTE) studies.Methods: ORAL Sync was a 1?year, randomized, placebo?controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily(BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease?modifying antirheumatic drug. ORAL Sequel is an open?label LTE study(data?cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology(ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28?4 [ESR]). Patient? and physician?reported outcomes: Health Assessment Questionnaire?Disability Index(HAQ?DI), Patient and Physician Global Assessment of Arthritis, and pain(visual analog scale). Safety was assessed throughout.Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20(tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28?4(ESR) <2.6(tofacitinib 5 mg BID, 7.1%;10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ?DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib?treated patients were similar to the global population.Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate?to?severely active RA up to Month 48. The safety profile was consistent with the global population.Clinical Trial Identifier: NCT00856544 and NCT00413699.

ILIF7 Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population： A Case-Control Study

Background： Interleukin （IL）-37, also called ILl F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis （RA）. This study aimed to investigate the role oflL1F7 gene polymorphism in RA susceptibility in a large cohort of patients. Methods： Five selected single-nucleotide polynaorphisms in IL 1F7 genes （rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270） were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender. Results： Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I （160 patients with RA： 252 healthy controls）. Further validation in Stage II comprised 730 unrelated patients with RA （mean age： 54.9 ± 12.6 years; 81.6% females） and 778 unrelated healthy individuals （mean age： 53.5 ± 15.7 years; 79.5% females）. No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions. Conclusion： 1L1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Hart population.

Factors relating to bone mineral density in young and middle-aged patients with ankylosing spondylitis

Background:Ankylosing spondylitis(AS)is a common chronic progressive rheumatic disease.The aim of this study was to explore factors influencing abnormal bone mineral density(BMD)in young and middle-aged patients with AS.Methods:From July 2014 to August 2018,hospitalized patients with AS and health examinees in the health examination center of our clinics,ranging in age from 20 to 50 years,were monitored.The BMD of the lumbar spine and femoral neck of AS patients and those of a healthy control group were measured using dual-energy X-ray absorption.The BMDs of AS patients were compared with respect to age,course of disease,iritis,smoking habits,sex,height,weight,body mass index(BMI),medication use,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),platelet volume,platelet count,uric acid(UA),alkaline phosphatase(AKP),and calcium ion levels.Single-nucleotide polymorphisms(SNPs)related to BMD were screened using genome-wide association analysis.Results:There was no statistical difference in the proportion of abnormal bone masses between the different body parts.The BMD of all bones in AS patients was lower than that in healthy controls(P<0.05).Additionally,BMD was correlated with serum calcium and CRP in AS patients(P<0.05),but not with age,platelet volume,platelet count,ESR,UA,AKP,height,weight,and BMI.The incidence of abnormal bone mass in AS patients was correlated with sex(P<0.05),but not with medication use,iritis,or smoking.BMD of the lumbar spine in AS patients did not correlate linearly with the course of the disease,but BMD of the femoral neck correlated linearly with the course of the disease(P<0.05).BMD was correlated with multiple SNPs in patients with AS.Lumbar BMD was correlated with rs7025373 and rs7848078.Femoral head BMD was correlated with 3:102157365,3:102157417,rs1252202,rs1681355,rs3891857,rs7842614,and rs9870734,suggesting that genetic factors play a role in BMD in patients with AS.Conclusions:The proportion of abnormal bone mass in AS patients was higher than that in healthy individuals of the same age.The factors related to BMD in patients with AS are gender,CRP,and blood calcium.The BMD of the femoral neck of AS patients decreases with the course of the disease,but BMD of the lumbar spine is not related to the course of the disease.BMD in AS patients is associated with multiple SNPs.

Effect of Mechanical Stress in Combination with Verapamil on Levels of Aggrecan and ADAMTS-5 mRNAs and Proteins in Human Osteoarthritic Chondrocyte/Agarose Constructs

To the Editor： Osteoarthritis （OA） has the highest prevalence and economic impact among arthritic maladies and is the most common cause of long-term disability among individuals over 65 years of age. OA is characterized by the degeneration of articular cartilage and the loss of cartilage matrix in affected joints. It is widely accepted that an imbalance between the biosynthesis and the degradation of extracellular matrix （ECM） occurs in OA cartilage.